Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Keratinocyte growth factor (KGF), a member of the fibroblast growth factor (FGF) family (and alternatively designated FGF-7), is a paracrine growth factor produced by mesenchymal cells and mitogenic specifically for epithelial cells. The potential effect of KGF on wound healing was assessed in vitro by measuring randomized migration and plasminogen activator (PA) activity of keratinocytes in response to the growth factor. Incubation of normal human keratinocytes with KGF in modified MCDB 153 medium significantly stimulated cell migration and PA activity compared with control (p < 0.001 and p < 0.01, respectively). When tested in these assays on an equimolar basis, 1 nM KGF was at least as potent as transforming growth factor alpha and more active than basic FGF. None of these effects were observed when KGF was administered to fibroblasts or endothelial cells. Stimulation of keratinocyte migration by KGF was dose dependent, and a neutralizing monoclonal antibody against KGF reduced KGF-stimulated migration and cell growth. Zymographic analyses of cell extracts and conditioned medium from KGF-treated keratinocytes revealed increased PA activity, which was mainly attributable to an elevated level of urokinase-type PA. These in vitro results suggest that KGF may have an important role in stimulating reepithelialization during the process of wound repair.
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PMID:Keratinocyte growth factor (FGF-7) stimulates migration and plasminogen activator activity of normal human keratinocytes. 833 Dec 96

Keratinocyte growth factor (KGF) is expressed by uterine endometrial epithelial cells during the estrous cycle and during pregnancy in pigs, whereas KGF receptor is expressed in conceptus trophectoderm and endometrial epithelia. In particular, KGF expression in the endometrium is highest on day 12 of pregnancy. This corresponds to the period of maternal recognition of pregnancy in pigs, which is signaled by large amounts of estrogen secreted by conceptus trophectoderm acting on the endometrium. Our hypothesis is that estrogens of conceptus origin stimulate endometrial epithelial KGF expression, and, in turn, secreted KGF stimulates proliferation and differentiation of conceptus trophectoderm. To determine the factors affecting KGF expression in the uterus, endometrial explants from gilts on day 9 of the estrous cycle were cultured in the presence of 17beta-estradiol, catechol estrogens, or progesterone. 17beta-Estradiol stimulated the expression of KGF (P < 0.05), whereas catechol estrogens had no effect (P > 0.05). Between days 9 and 15 of pregnancy, proliferating cell nuclear antigen was abundant in conceptuses, but was barely detectable in uterine endometrial epithelia. To determine the effects of KGF on conceptus trophectoderm, porcine trophectoderm (pTr) cells were treated with recombinant rat KGF (rKGF). rKGF increased the proliferation of pTr cells (P < 0.01) as measured by [(3)H]thymidine incorporation. rKGF elicited phosphorylation of KGF receptor and activated the mitogen-activated protein kinase (ERK1/2) cascade in pTr cells. pTr cell differentiation was affected by rKGF, because it increased expression of urokinase-type plasminogen activator, a marker for differentiation in pTr cells. Collectively, these results indicate that estrogen, the pregnancy recognition signal from the conceptus in pigs, increases uterine epithelial KGF expression, and, in turn, KGF stimulates the proliferation and differentiation of conceptus trophectoderm.
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PMID:Keratinocyte growth factor is up-regulated by estrogen in the porcine uterine endometrium and functions in trophectoderm cell proliferation and differentiation. 1135 76

Keratinocyte growth factor (KGF)/fibroblast growth factor-7 (FGF-7) is a paracrine- and epithelium-specific growth factor produced by cells of mesenchymal origin. It acts exclusively through FGF-7 receptor (FGFR2/IIIb), which is expressed predominantly by epithelial cells, but not by fibroblasts, suggesting that it might function as a paracrine mediator of mesenchymal-epithelial interactions. KGF/FGF-7 plays an essential role in the growth of epithelial cells and is frequently overexpressed in cancers of epithelial origin such as pancreatic cancer, switching paracrine stimulation of KGF/FGF-7 to an autocrine loop. Less is known, however, about the signaling pathways by which KGF/FGF-7 regulates the response of epithelial cells. To delineate the signaling pathways activated by KGF/FGF-7 and examine cellular response to KGF/FGF-7 stimulation, we performed functional analysis of KGF/FGF-7 action. In this report, we show that KGF/FGF-7 activated nuclear factor kappaB (NF-kappaB), which in turn induced expression of VEGF, MMP-9, and urokinase-type plasminogen activator and increased migration and invasion of KGF/FGF-7-stimulated human pancreatic ductal epithelial cells. Expression of phosphorylation-defective IkappaBalpha (IkappaBalphaS32A,S36A), which blocked NF-kappaB activation, inhibited KGF/FGF-7-induced gene expression and cell migration and invasion. Our results demonstrate for the first time that KGF/FGF-7 induces NF-kappaB activation and that NF-kappaB plays an essential role in regulation of KGF/FGF-7-inducible gene expression and KGF/FGF-7-initiated cellular responses. Thus, these findings identify one signaling pathway for KGF/FGF-7-regulated cell migration and invasion and suggest that paracrine sources of KGF/FGF-7 are one of the malignancy-contributing factors from tumor stroma.
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PMID:Keratinocyte growth factor/fibroblast growth factor-7-regulated cell migration and invasion through activation of NF-kappaB transcription factors. 1720 Jan 10